Infectious Disease Flashcards
Volume of distribution
Drug must reach the sites of infection at adequate concentrations
Factors: Lipid solubility, tissue penetration, blood flow to tissues, pH, plasma protein binding
Tetracyclines have…
Great distribution to the tissue, do not stay in the blood stream. Not good to treat blood stream infections
Metabolism
Most are metabolized in the liver
CYP450: Macrolides, rifampin, sulfonamides…
Elimination
Renal and non renal
Some drugs: Vancomycin, zosyn need different dosing based on GFR
Absorption
Many routes of intake
IM, inhalation, IV, PO, Intraperitoneal, Intrathecal
Agents that are active against the cell wall…
B-lactams, Vancomycin, Daptomycin, Telavancin, Azoles
Antibiotics that are protein synthesis inhibitors…
Tetracyclines (3oS)
Macrolides, clindamycin, chloramphenicol, synercid (5oS)
Fluoroquinolones (DNA girasse, Topoisomerase)
Rifamycins (RNA polymerase)
Linezolid (Other ribosomal agents)
Antibiotics that are cationic detergents that dissolve the cell wall…
Polymyxins
Antibiotics that inhibit free radical formation…
Metronidazole
Antimicrobial resistance
Drug enzymatic inactivation
Altered target site
Decreased permeability of antibiotic into cell
What is bacteriostatic?
Inhibits growth and replications
What is bactericidal?
Cause bacterial cell death
MIC?
Minimum Inhibitory Concentration (for bacteriostatic)
MBC?
Minimum Bactericidal Concentration
Concentration dependent antibiotics..
Peak matters, time above the MIC doesn’t matter.
Aminoglycosides, Daptomycin, Flouroquinolones
Time dependent killing
More time above MIC, the better they kill. Peak doesn’t matter.
B-Lactams
Linezolid
A combination of concentration and time dependent killing
Vancomycin, Macrolides, Tetracyclines, azoles
B-Lactam antibiotics properties
Inhibit cell wall synthesis
Bactericidal
Time-dependent killing
B-Lactam antibiotics
Penicillins
Cephalosporins
Carbapenems
Monobactams
Penicillin antimicrobial spectrum
Gram positive
Primarily Streptococci
Gram negative, very few
Neisseria Meningitidis
Drug of choice for:
Actinomyces (found in mouth)
Syphillis (T. Pallidum)`
“Anti-staphylococcal” penicillins
Methicillin Oxacillin Nafcillin Dicloxacillin Cloxacillin
Mostly for MSSA
Soft tissue/skin infections
Gram negative rods SPACE bugs…
S-Serratia, Klebsiella, Enterococcus P-Proteus vulgaris or Pseudomonas A-Acromobacter or Acinetobacter C-Citrobacter E-Enterrobacter
“Low resistance” GNR…
Aminopenicillins
Aminopenicillin antimicrobial spectrum…
Gram negative with “low resistance” enterobacteriacae
H. Influenzae
Food-derived:
Listeria (DOC)
Salmonella and Shigella
Gram +, Streptococci and enterococci
Better anaerobic coverage
Extended spectrum penicillins
Carboxypenicillins (Ticarcillin)
Ureidopenicillins
(Piperacillin)
Rarely used as single agents in US
Extended spectrum antimicrobial spectrum
Gram negative, increased activity including pseudomonas
Gram Positive, overall less, but still effective
Excellent anaerobic activity
B-Lactamase inhibitors
Clavulanic acid
Sulbactam
Taxobactam
Not used as single agents in the US
Cross-reactivity with other B-Lactams
1st gen. cephalosporins 5-10%
2 & 3 gen. Cephalosporins 1-5%
Carbapenems 1-5%
Monobactams, rare
How many generations of Cephalosporins
5
The first generations have only…
and as you move to the 5th generations they become more…
Gram positive
Gram negative also
Colonization is…
the presence and replication of micro organisms without tissue invasion and/or damage
Normal Flora of the nasopharynx
Streptococci Haemophilus Neisseria Mixed anaerobes Candida Actinomyces
Normal Flora of the Skin
Staphylococci Streptococci Corynebacteria Proprionibacteria Yeasts
Normal Flora of the upper bowel
Enterobacteriaceae
Enterococci
Candida
Normal Flora of the Lower bowel
Bacteroides
Bifidobacteria
Clostridium
Peptostreptococci
Normal flora of the vagina
Lactobacilli Streptococci Corynebacteria Candida Actinomyces Mycoplasma hominid
Innate immune system of eyes
Lysozyme in tears kills gram positive bacteria
Innate immune system of the nose
Removal of particles by turbinates and humidification
Innate immune system of the upper airway
Mucus and cilia capture organisms and remove them
Innate immune system of the skin
physical barrier
Innate immune system of the stomach
Stomach acid kills ingested pathogens
innate immune system of the bowel
Competition and toxic products from intestinal flora
innate immune system of the bladder
Flushing action of urinary flow removes organisms
innate immune system of the vagina
Low vaginal pH from lactobacilli prevents colonization by pathogens
Innate immune system of the whole body
molecular and cellular defense
Patter recognition molecule
Neutrophils
Macrophages
Infection is an invasive presence and replication of micro-organisms accompanied by…
Local cell injury/death
Secretion of toxins
Host immune response
Culture interpretation is dependent upon:
Complete clinical picture
Method of collection
Gram stain results
Cellular evidence
Most likely cause of contamination…
Poor collection technique
Gram positive Cocci
Staphylococcus
Streptococcus
Enterococcus
Gram positive Rods
Corynebacterium
Bacillus
Listeria
Gram Negative Cocci
Neisseria
Moxorella catarrhalis
Gram negative rods
Enterobacteriaciae Normal gut flora Vibrio Shigella Salmonella Pseudomonas Hemophilus
Anaerobes
Gut flora
Actinomyces
Bacteriodes
Mycobacteria
TB
Fungi
Candida
Aspergillus
Viruses
Herpesvirus family
Adenovirus
Influenza
Coxsackievirus
Rickettsia
Rocky Mountain Spotted Fever
Parasites
Giardia Lamblia
Pneumocystis Jiroveci
Spirochetes
Treponema Pallidum
Principles of antimicrobial Coverage
The use of any antibiotic promotes resistance
Broad spectrum is used- promotes resistance to both normal and pathogenic flora
Narrow spectrum- confines resistance to fewer organisms
Therapeutic considerations of antimicrobial coverage
Identify whether infection is present
Choose the narrowest spectrum, least toxic, least invasive, and least expensive medication that is the most effective
Primary interventional concepts of antimicrobial coverage
Observation without antibiotics
Preventive/Prophylactic therapy- patients with artificial heart valve who need dental work
Empiric therapy- what we use while we await cultures
Specific therapy- tailored to the cultures
Meningitis common bacterial organisms
Strep Pneumonia
Neisseria meningitidis
Gram negative, group B strep more common in > 50 years
Meningitis common viral organisms
HSV
EBV
Varicella Zoster
Coxsackievirus
Meningitis clinical manifestations
HA and fever AMS Nuchal rigidity Positive Kernig and Brudzinskis May also see photophobia and seizures
Kernigs sign
Hip flexion on supine patient, hamstrings contract and they are unable to extend their knees
Brudzinskis sign
Head flexion causes spontaneous hip and knee flexion
Meningitis diagnosis
CT scan
CSF for gram stain, culture, AFB
Blood cultures
CT must be done before LP because you can cause herniation is symptoms are caused by space occupying lesion
Bacterial Meningitis LP
Leukocytes- 100-50000 PMN
Protein- 100-500
Glucose- Low
Viral Meningitis LP
Leukocytes- less than 1000 MN
Protein 50-200
Glucose normal or high
Viral encephalitis LP
Leukocytes- less than 1000 PMN early then MN
Protein 50-200
Glucose- normal or high
TB meningitis LP
Leukocytes- 10-500 lymphocytes
Protein- 100-500
Glucose Low < 40
Brain Abscess
Leukocytes- 10-200 lymphocytes
Protein 100-500
Glucose Normal
Meningitis treatment
Antibiotics
Need bactericidal medication
Drugs that readily cross the BBB
Dexamethason prior to abs, then Q 6h
Ceftriaxone + Vancomycin (18-50 y.o community acquired)
Add ampicillin if > 50
Continue for 10-14 days
Meningitis treatment other
Avoid volume overload
seizure precautions
monitor for cerebral edema
ID consult
If meningococcal meningitis is diagnosed
Prophylactic treatment is indicated for anyone with close contact
College setting
Viral meningitis treatment
Self-limiting
Treatment directed towards the specific virus
Endocarditis risk factors
Native heart valve disease in those > 60 years
Prosthetic heart valves
IV drug Abuse (tricuspid valve)
Bacteremia following dental (streptococci), pulmonary, urologic or lower GI procedures
Endocarditis common organisms
S. Aureus is the MOST COMMON!!! Streptococci Enterococci Coag negative staphylococci HACEK organisms (pg 1458 CMDT) Fungi
Endocarditis Clinical manifestations
Persistent fever- days to weeks Malaise Fatigue Anorexia Arthralgias/Myalgias
New or worsening murmur
Petechiae, Osler (tender on pads fingers and toes)/janeway nodes (Contender erythematous macule on palms and feet), splinter hemorrhages
Roth spots
Splenomegaly
What are Osler nodes
Tender nodules on the pads of the fingers and toes
What are Janeway nodes?
Nontender erythematous macule on palms of the hands and soles of the feet
How to diagnose Endocarditis
BC x 3 at least an hour apart
TTE & TEE
CXR
Modified Duke criteria
What is the modified duke criteria?
Clinical criteria
2 major, 1 major + 3 minor or 5 minor
Major criteria
Positive blood culture for characteristic organism or persistently positive
Echocardiographic identification of a valve related mass or abscess
New Valvular regurgitation
Minor criteria Predisposing heart lesion or IV drug Fever Vascular lesions Immunological phenomena Microbiologic evidence Echocardiographic findings consistent with but not diagnostic of endocarditis
Endocarditis treatment
Empiric treatment with Ceftriaxone and Vancomycin
Then tailor therapy for culture
ID and Cardiology consult
Surgical intervention if treatment failure after 7-10 days or acute HF
Tailored treatment of endocarditis
Streptococci -PCN or Ceftriaxone
Enterococci- PCN/Ampicillin and Gentamycin
MSSA/MRSA- Nafcillin/Oxacillin or Cefazolin; Vancomycin/Daptomycin
Coag negative staph (Prosthetic valves)- Vancomycin, Rifampin, Gentamycin
HASEK- Ceftriaxone
Dental prophylaxis
Amoxicillin is preferred
Alternative for PCN allergy is Clindamycin, Cephalexin, Azithromycin
Endocarditis complications
Myocardial abscess
Rhythm disturbances
Embolization- septic emboli to brain, coronary arteries, spleen
TV endocarditis- septic pulmonary emboli with IVDA
CLABSI risk factors
Healthcare associated infection
Central lines placed in the femoral artery- 72%
CLABSI clinical manifestations
Fever
Purulent drainage from the site
No other readily available source
CLABSI common organisms
Coag negative staph (most common) MRSA E. Faecium Pseudomonas Acinetobacter Candida
CLABSI antibiotic empiric treatment
Ceftazidine or Cefepime plus Vancomycin
CLABSI management
ABX
Remove lines
Culture tip
Blood cultures
Pneumonia Types
Community associated (CAP) Ventilator associated (VAP) Hospital associated (HAP) Healthcare associated (HCAP)
Pneumonia common organisms
CAP- S. Pneumonia (most common), Klebsiella, S. Aureus, H. Influenzae
VAP/HAP/HCAP- MRSA (most common), P. Aeruginosa (often MDR), Acinetobacter, E. Coli, Enterobacter
Atypical- M. Pneumonia, Legionella
Viral
Pneumonia clinical manifestations
- CAP- fever, cough, may have sputum or dyspnea, chills, diaphoresis, pleurisy, anorexia, HA, Fatigue, Myalgias
- VAP/HAP/HCAP- the presence of a new infectious infiltrate on CXR with new onset fever, sputum production, leukocytosis, and reduced SaO2
- PE findings- Tachypnea, ST, Crackles, or diminished breath sounds
Urinary antigen for S. pneumoniae and legionella pneumophilia-
reserved for severe cases of CAP in the ICU
CAP management
outpatient, healthy, no recent abx
a. Macrolide or doxycycline
CAP management outpatient with comorbid conditions
a. Resp. FQ (Levaquin)
b. PO beta lactam and macrolide
CAP management
Inpatient, nonicu
a. IV betalactam + macrolide
b. Resp. FQ (Levaquin)
CAP management
inpatient, ICU
a. IV beta lactam + macrolide
b. IV beta lactam + Resp FQ
HAP treatment
- Use 2 drugs if (antipseudo + a Fluroquinalone or an aminoglycoside)
a. prior IV abx last 90 days
b. Structural lung disease
c. Septic shock or MV need - AntiMRSA coverage is required if…
a. Staph isolates
b. Prior IV ABX last 90 days
c. Septic shock or MV
HAP antipseudomonal treatment
- Antipseudomonal beta lactam
a. Zosyn
b. Cefepime
c. Meropenem
d. Imipenem
Plus 1 of the following: - Resp. FQ
a. Levofloxacin
b. Ciprofloxacin - AG
a. Gentamycin
b. Tobramycin
c. Amikacin
HAP MRSA treatment
- Antipseudomonal beta lactam
a. Zosyn
b. Cefepime
c. Meropenem
d. Imipenem
Plus Add 1:
Vancomycin
Linezolid
VAP treatment
- Antipseudomonal ABX needed if
a. > 10% GNR resistance
b. Structural lung disease
c. Risk factors for MDR VAP - MRSA ABX needed if
a. > 10-20% isolates MRSA
b. Risk factors for MDR VAP
VAP antipseudomonal treatment
- Antipseudomonal beta lactam
a. Zosyn
b. Cefepime
c. Meropenem
d. Imipenem
Plus 1 of:
a. FQ: Levo, Cipro
b. AG: amikacin, gent. Tobra
c. Polymyxin: Colistin
VAP MRSA treatment
- Antipseudomonal beta lactam
a. Zosyn
b. Cefepime
c. Meropenem
d. Imipenem
Plus 1 of:
Vancomycin or Linezolid
Risk factors for MDR
Antimicrobial therapy in previous 90 days
Current hospitalization of > 5 days
Immunosuppressive disease and or therapy
Other: Previous hospitalization within last 90 days Resides in nursing home Home infusion therapy Chronic dialysis Home wound care Family members with MDR
Urinary tract infection risk factors
Indwelling catheters
females
UTI common organisms
- E. Coli, Klebsiella, Proteus miribilis
+ S. saprophytic, E. Faecalis, GB strep
Uncomplicated cystitis ABX
Nitrofurantoin Bactrim Fosfomycin Fluoroquinolones AMX Cefdinir, Cefaclor, Cefpodoxime
Uncomplicated pyelonephritis ABX
Fluoroquinolones Levofloxacin Ciprofloxacin Bactrim Aminoglycosides +/- ampicillin Cephalosporin or penicillin +/- ahminoglycosides Carbapenems
Complicated cystitis ABX
Fluoroquinolones
Levofloxacin
Ciprofloxacin
Ampicillin or amoxicillin
Complicated pyelonephritis ABX
Fluoroquinolone plus cephalosporin or penicillin or carbapenem
Skin and soft tissue infections risk factors
Invasive devices
Surgical procedures
Debilitated skin integrity
Diabetics
Skin and soft tissue infection clinical presentation
Rapidly spreading area of erythema
Culture the site if appropriate
Can lead to sepsis
Assess for necrotizing fasciitis if areas of necrosis appear
Skin and soft tissue infection common organisms of necrotizing fasciitis
V. Vulnificis
S. Pyogenes
Aeromonas
Clostridiums
Skin and soft tissue infection ABX therapy for non purulent infections
Cellulitis
- penicillin
- ceftriaxone
- cefazolin
- clindamycin
If severe: rule out nec fasc. vancomycin plus zosyn
Skin and soft tissue infection treatment
May require surgical debridement
Skin and soft tissue infection ABX therapy for purulent infections
Mild- just I&D
Moderate- I&D plus C&S
-Bactrim or doxycycline
Once C&S:
MRSA- Bactrim
MSSA- Cephalexin or Dicloxacillin
Severe- I&D plus C&S
- Vancomycin
- Daptomycin
- Linezolid
- Televancin
- Ceftaroline
Once C&S: MSSA use: -Nafcillin -Cefazolin -Clindamycin
Defined ABX therapy for severe non purulent soft tissue infection
Streptococcus pyogenes- Penicillin plus clindamycin
Clostridial sp. - penicillin plus clindamycin
Vibrio vulnificus- Doxycycline plus ciprofloxacin
Polymicrobial
Vanco plus Zosyn
Clinical manifestations of necrotizing fascitis
Erythema Marked edema SEVERE tenderness Bullae formation Compartment syndrome Systemic symptoms- fever, septic shock
ABX coverage for nec. fasc
Vancomycin and Zosyn
Doxycycline and Ceftazidime are essential with a high degree of suspicion for Vibrio vulnificus
Surgical debridement is primary treatment
Surgical site infection risk factors
severity of illness type of surgery length of surgery comorbidities age steroids other infected sites
Surgical site infection clinical manifestations
Fever
evidence of local infection- redness, drainage, poor healing
(Culture drainage)
Surgical site infection treatment
Determined by gram stain and culture
Treat for common skin flora in that area
Osteomyelitis risk factors
Diabetes and diabetic foot wounds
Injured bone that has lost vascularity- no longer accesses to blood borne defenses
Osteomyelitis common organisms
S. Aureus
Coag negative staphylococcus
Osteomyelitis management
Orthopedic referral
MRI
Culture of open site or surgical bone biopsy
Drainage is the central concept of therapy- ABX are an adjunct
may require many months of therapy
C. Diff colitis risk factors
Antibiotic use- primarily fluoroquinolone, clindamycin and cephalosporins
Age > 65
Hospitalization
Severe illness
C. Diff
Anaerobic gram + spore forming bacillus
C. Diff managment
Prevention of transmission is essential
C. Diff ABX
Metrondiazole
Add vancomycin PO for severe disease
10-14 days
C. Diff clinical manifestations
Colitis with diarrhea Watery, foul smelling abdominal pain/crampin fever anorexia nausea malaise fever shock leukocytosis renal failure
C. Diff treatment
DC offending antibiotics
GI/ID consult
ABX
Fecal transplants
Fever of unknown origin definition
Fever > 101 for at least 3 weeks
Definitive cause occult despite complete workup
FUO common etiologies
Infection malignancy autoimmune disease- 22% Drug induced Granulomatous disease Any inflammatory process- surgery, burns, trauma Factious fever
FUO treatment well appearing
Stop non essential meds CBC BMP LFT UA Radiographs as needed Observation
FUO treatment is appearing ill
Admit to hospital Stop non essential meds LFT hepatitis panel BC UA CSF culture CRP
FUO workup for suspected infectious cause
Cultures
CSF studies
CRP/ESR
Empiric antibiotics
FUO workup for suspected oncologic cause
Uric acid Lactate dehydrogenase Ferritin Peripheral smear Chest radiograph Hold steroids
FUO workup for suspected autoimmune cause
Antinuclear antibody Rheumatoid factor C3, C4, CH50 Thyroid function CRP ESR Ferritin
FUO workup for suspected immunodeficiency causes
immunoglobulins
lymphocyte markers
consider antibody titers to known vaccinations
HIV
